US3705151A - Benzene-sulfonyl semicarbazides and process for preparing them - Google Patents
Benzene-sulfonyl semicarbazides and process for preparing them Download PDFInfo
- Publication number
- US3705151A US3705151A US750747A US3705151DA US3705151A US 3705151 A US3705151 A US 3705151A US 750747 A US750747 A US 750747A US 3705151D A US3705151D A US 3705151DA US 3705151 A US3705151 A US 3705151A
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- US
- United States
- Prior art keywords
- benzenesulfonyl
- ethyl
- melting point
- indoline
- iso
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- LSNDGFYQJRXEAR-UHFFFAOYSA-N benzenesulfonamidourea Chemical class NC(=O)NNS(=O)(=O)C1=CC=CC=C1 LSNDGFYQJRXEAR-UHFFFAOYSA-N 0.000 title description 12
- 238000004519 manufacturing process Methods 0.000 title 1
- -1 BENZENE-SULFONYL SEMICARBAZIDES Chemical class 0.000 abstract description 58
- 229910052736 halogen Inorganic materials 0.000 abstract description 9
- 150000002367 halogens Chemical class 0.000 abstract description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract description 3
- NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 abstract description 2
- POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical compound N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 abstract description 2
- PDELQDSYLBLPQO-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-indole Chemical compound C1CCCC2NCCC21 PDELQDSYLBLPQO-UHFFFAOYSA-N 0.000 abstract description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 2
- 230000002218 hypoglycaemic effect Effects 0.000 abstract description 2
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical class F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 238000002844 melting Methods 0.000 description 60
- 230000008018 melting Effects 0.000 description 60
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 47
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000004202 carbamide Substances 0.000 description 19
- 235000013877 carbamide Nutrition 0.000 description 18
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 11
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- ALZKZGUTVJXYEF-UHFFFAOYSA-N benzenesulfonylcarbamic acid Chemical class OC(=O)NS(=O)(=O)C1=CC=CC=C1 ALZKZGUTVJXYEF-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 150000002429 hydrazines Chemical class 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- RDEGOEYUQCUBPE-UHFFFAOYSA-N 3-ethoxythiophene Chemical compound CCOC=1C=CSC=1 RDEGOEYUQCUBPE-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- JWPWVPPTDSULMI-UHFFFAOYSA-N benzenesulfonamidothiourea Chemical class NC(=S)NNS(=O)(=O)C1=CC=CC=C1 JWPWVPPTDSULMI-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- AOCYHPQXGJBAQQ-UHFFFAOYSA-N ethyl n-sulfonylcarbamate Chemical compound CCOC(=O)N=S(=O)=O AOCYHPQXGJBAQQ-UHFFFAOYSA-N 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- FCXSGAKSWAEXPU-UHFFFAOYSA-N iminocarbamic acid Chemical class OC(=O)N=N FCXSGAKSWAEXPU-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003349 semicarbazides Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- FDPGUECLKNPLOB-UHFFFAOYSA-N (n-phenylanilino)urea Chemical class C=1C=CC=CC=1N(NC(=O)N)C1=CC=CC=C1 FDPGUECLKNPLOB-UHFFFAOYSA-N 0.000 description 1
- ASRMWYDEZPXXBA-UHFFFAOYSA-N (sulfonylamino)urea Chemical class NC(=O)NN=S(=O)=O ASRMWYDEZPXXBA-UHFFFAOYSA-N 0.000 description 1
- BZYUMXXOAYSFOW-UHFFFAOYSA-N 2,3-dimethylthiophene Chemical compound CC=1C=CSC=1C BZYUMXXOAYSFOW-UHFFFAOYSA-N 0.000 description 1
- RFSKGCVUDQRZSD-UHFFFAOYSA-N 3-methoxythiophene Chemical compound COC=1C=CSC=1 RFSKGCVUDQRZSD-UHFFFAOYSA-N 0.000 description 1
- WSYLHHOFEDCQKY-UHFFFAOYSA-N 5-(benzenesulfonyl)-1h-imidazole-2-carboxamide Chemical class N1C(C(=O)N)=NC(S(=O)(=O)C=2C=CC=CC=2)=C1 WSYLHHOFEDCQKY-UHFFFAOYSA-N 0.000 description 1
- GFEQSVKCVJWGST-UHFFFAOYSA-N 5-chlorothiophene Chemical compound ClC1=C=C[CH]S1 GFEQSVKCVJWGST-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- YPTCXHDMBCRXHL-UHFFFAOYSA-N NC(=O)N.C1NCCC2=CC=CC=C12 Chemical compound NC(=O)N.C1NCCC2=CC=CC=C12 YPTCXHDMBCRXHL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 150000008331 benzenesulfonamides Chemical class 0.000 description 1
- JOMVGRRCEIJQFK-UHFFFAOYSA-N benzenesulfonylcarbamothioic s-acid Chemical class OC(=S)NS(=O)(=O)C1=CC=CC=C1 JOMVGRRCEIJQFK-UHFFFAOYSA-N 0.000 description 1
- 150000001714 carbamic acid halides Chemical class 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003009 desulfurizing effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- MBTLHVYOEGCXPI-UHFFFAOYSA-N iminocarbamothioic s-acid Chemical class OC(=S)N=N MBTLHVYOEGCXPI-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- UJYAZVSPFMJCLW-UHFFFAOYSA-N n-(oxomethylidene)benzenesulfonamide Chemical class O=C=NS(=O)(=O)C1=CC=CC=C1 UJYAZVSPFMJCLW-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/72—4,7-Endo-alkylene-iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/08—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with a hetero atom directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/28—Nitrogen atoms
- C07D295/32—Nitrogen atoms acylated with carboxylic or carbonic acids, or their nitrogen or sulfur analogues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Definitions
- R represents (a) a 3,fl-endoethylene-hexamethylene imine or a corresponding cyclic system having a C -C double linkage
- the present invention provides benzene-sulfonyl semicarbazides of the formula and definition set forth in the abstract.
- the new semicarbazides and their salts are valuable medicinal agents distinguished by a strong and particularly long-lasting blood-sugar lowering activity.
- R represents a phenyl group substituted in 2-position by lower alkoxyor alkenoxy and in 4- or S-position by a halogen atom or by a lower alkyl or alkoxy.
- the present invention further relates to a process for 3,705,151 Patented Dec. 5,, 1972 ICC preparing said benzenesulfonyl semicarbazides.
- methods for preparation there may be mentioned the following methods:
- the benzenesulfonyl semicarbazides obtained may then be converted, if desired, into their salts by treatment with alkaline agents or with physiologically tolerable inorganic or organic acids.
- benzenesulfonyl ureas which may be unsubstituted at the terminal nitrogen atom, or substituted once or twice by alkyl or aryl groups, may be converted into the final products by reacting these with hydrazines of the formula R NH if desired, in the form of their salts.
- benzenesulfonyl ureas substituted in this manner there may be used the corresponding N-benzenesulfonyl-N-acyl ureas, benzene-sulfonyl-carbamoyl-imidazols, benzenesulfonyl-carbamoylpyrazols or benzene-sulfonyl-carbamoyl-triazols or bis- (benzenesulfonyD-ureas which carry at one of the nitrogen atoms another substituent, for example methyl.
- Such bisbenzenesulfonyD-ureas or N-'benzene-sulfonyl-Nacylureas may be treated with hydrazines of the formula R NH and the salts obtained may be heated to elevated temperatures, preferably to at least C.
- the imino-carbamic acid esters or benzenesulfonyl carbamic acid esters mentioned, as well as the corresponding thioesters, contain in the ester component preferably an alkyl radical of low molecular weight or a phenyl radical.
- the benzenesulfonyl isosemicarbazide ethers, -isothiosemicarbazide ethers or -parabanic acids, used as starting materials, may be obtained by reacting corresponding isosemicarbazide ethers, isothiosemicarbazide ethers or parabanic acids with corresponding benzenesulfochlorides.
- Benzenesulfonyl isosemicarbazide ethers are also obtained, in the first place, by desulfurizing benzenesulfonyl thiosemicarbazides in methanol. They are subsequently converted into benzenesulfonyl semicarbazides by hydrolysis.
- the one or the other of the previously described methods may prove unsuitable for preparing the individual compounds falling under the general formula, or at least will make it necessary for active groups to be protected. Such relatively rare cases can easily be recognized by the expert, and there is no difficulty in successfully applying another one of the syntheses described.
- the process embodiments of the present invention may in general, vary within wide limits and may be adapted to each individual case.
- the reactions can be efiected with the use of solvents, at room temperature or at an elevated temperature.
- radical R may be mentioned, for example, the following groups:
- the sulfonyl-semicarbazide derivatives obtainable according to the present invention are valuable medicinal agents which are distinguished by a strong action of lowering the blood sugar level. This applies, in particular,
- R represents a phenyl radical 75 l I 01 OH a TABLE Lowering of the blood sugar level in rabbits after ad- Limit amount ministering 10 causing lowermgJkg. per os ing of the after blood sugar level in 3 hours, 24 hours, rabbits, Compound percent percent mg./kg.
- the toxicities of the products of the invention are very low, they are within the range of the above-mentioned N-(4-methy1 benzenesulfonyl)-N'-n-butyl-urea which is very well tolerable.
- the products of the present invention into orally administerable preparations which have blood sugar lowering action and which can accordingly be used in the treatment of diabetes mellitus; these can be employed as such or in the form of their salts or in the presence of substances causing salt formation.
- salt formation there can be used, for example, alkaline agents such as alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkaline earth metal carbonates, alkali metal bicarbonates and alkaline earth metal bicarbonates or physiologically tolerated acids.
- the pharmaceutical preparations are preferably in the form of tablets which contain, in addition to the compounds of the present invention, the usual adjuvants and carriers such as talc, starch, lactose, tragacanth, magnesium stearate and the like.
- EXAMPLE 1 4 [4 (B 2-methoXy-5-chlorobenzamino -ethyl)- benzenesulfonyl] 1,1 (2,5-endoethylene-hexamethylene)-semicarbazide 4.2 grams of N [4 (B- 2-methoxy-5-chlorobenzamido ethyl) benzenesulfonyl] methyl-urethane (melting point l89l9l C.) were suspended in 75 milliliters of dioxane and 1.6 grams of 1,1-(2,5-endoethylenehexamethylene)-hydrazine were added thereto. The mixture was heated to 110 C.
- composition from methanol/dimethylformamide from N [4 (B 3 ethoxythiophene 2 carbonamido ethyl) benzenesulfonyl] methylurethane (melting point 163-l65 C.) N [4 (B 3 ethoxythiophene 2 carbonamido ethyl) benzenesulfonyl] N decahydroquinolino urea, melting point 186-187" C. (form methanol/dimethylformamide);
- N [4 (B 2 methoxybenzamido ethyl)- benzenesulfonyl] methylurethane (melting point 174- 176 C.)
- N [4 (B 2 methoxy-5-methyl-benzamido ethyl) benzenesulfonyl] ethylurethane (melting point 166l70 C.)
- N [4 (,6 2 methoxy 5 methylbenzamido ethyl) benzenesulfonyl] N 3-azaspiro [5,5] undecyl 3) urea (melting point 171- 173 C.);
- N [4 (5 2 methoxy 5 fluoro-benzamido ethyl) benzenesulfonyl] ethylurethane (melting point 123 C.)
- N [4 (5 4 chloro-benzamido -ethyl)-benzenesulfonyl] N (4,7 methano hexahydro-isoindolino 2) urea, melting point 203.5-205.5 C. (from dilute methanol/dioxane);
- thienyl which may carry one or two substituents selected from the group consisting of halogen, lower alkyl, or lower alkoxy,
- Y represents -CH CH -CH -CH--(CH or -CH(CH )--CH and R represents B,fl-endoethylene-hexamethylene-imine.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF0053221 | 1967-08-12 | ||
| US75074768A | 1968-08-07 | 1968-08-07 | |
| US00259299A US3847938A (en) | 1967-08-12 | 1972-06-02 | Benzene-sulfonyl semicarbazides and process for preparing them |
| US00259300A US3843661A (en) | 1967-08-12 | 1972-06-02 | Benzene-sulfonyl semicarbazides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3705151A true US3705151A (en) | 1972-12-05 |
Family
ID=27436967
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US750747A Expired - Lifetime US3705151A (en) | 1967-08-12 | 1968-08-07 | Benzene-sulfonyl semicarbazides and process for preparing them |
| US00259300A Expired - Lifetime US3843661A (en) | 1967-08-12 | 1972-06-02 | Benzene-sulfonyl semicarbazides |
| US00259299A Expired - Lifetime US3847938A (en) | 1967-08-12 | 1972-06-02 | Benzene-sulfonyl semicarbazides and process for preparing them |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00259300A Expired - Lifetime US3843661A (en) | 1967-08-12 | 1972-06-02 | Benzene-sulfonyl semicarbazides |
| US00259299A Expired - Lifetime US3847938A (en) | 1967-08-12 | 1972-06-02 | Benzene-sulfonyl semicarbazides and process for preparing them |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US3705151A (enrdf_load_stackoverflow) |
| AT (1) | AT326139B (enrdf_load_stackoverflow) |
| BE (1) | BE719374A (enrdf_load_stackoverflow) |
| CA (1) | CA961853A (enrdf_load_stackoverflow) |
| CH (4) | CH522611A (enrdf_load_stackoverflow) |
| FR (2) | FR1585642A (enrdf_load_stackoverflow) |
| GB (1) | GB1230651A (enrdf_load_stackoverflow) |
| LU (1) | LU56669A1 (enrdf_load_stackoverflow) |
| NL (1) | NL6811449A (enrdf_load_stackoverflow) |
| OA (1) | OA02879A (enrdf_load_stackoverflow) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3897452A (en) * | 1974-08-19 | 1975-07-29 | Merck & Co Inc | Substituted 1,4-dihydro(and 1,2,3,4-tetrahydro)-naphthalen-1,4-imines |
| US3983107A (en) * | 1973-12-05 | 1976-09-28 | Pfizer Inc. | Hypolipidemic alkenesulfonamides |
| US4025519A (en) * | 1972-08-07 | 1977-05-24 | Hoechst Aktiengesellschaft | Benzenesulfonyl-ureas |
| US4062960A (en) * | 1974-11-06 | 1977-12-13 | Pfizer Inc. | Hypolipidemic alkenesulfonamides |
| US4136180A (en) * | 1976-05-24 | 1979-01-23 | Pfizer Inc. | Hypolipidemic substituted styrenesulfonylureas |
| US4282239A (en) * | 1978-06-27 | 1981-08-04 | Hoechst Aktiengesellschaft | Sulfonyl ureas and pharmaceutical preparations thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4288454A (en) * | 1978-07-24 | 1981-09-08 | Hoffman-La Roche Inc. | Antiviral 1-adamantyl-3-(phenylsulfonyl)thioureas |
-
1968
- 1968-08-07 US US750747A patent/US3705151A/en not_active Expired - Lifetime
- 1968-08-07 LU LU56669D patent/LU56669A1/xx unknown
- 1968-08-08 CH CH387371A patent/CH522611A/de not_active IP Right Cessation
- 1968-08-08 CH CH387471A patent/CH522612A/de not_active IP Right Cessation
- 1968-08-08 CH CH1188868A patent/CH516536A/de not_active IP Right Cessation
- 1968-08-08 CH CH387571A patent/CH522613A/de not_active IP Right Cessation
- 1968-08-09 AT AT780068A patent/AT326139B/de not_active IP Right Cessation
- 1968-08-10 CA CA027,091A patent/CA961853A/en not_active Expired
- 1968-08-12 GB GB1230651D patent/GB1230651A/en not_active Expired
- 1968-08-12 NL NL6811449A patent/NL6811449A/xx unknown
- 1968-08-12 FR FR1585642D patent/FR1585642A/fr not_active Expired
- 1968-08-12 BE BE719374A patent/BE719374A/fr unknown
- 1968-08-12 OA OA53354A patent/OA02879A/xx unknown
- 1968-11-08 FR FR173084A patent/FR8231M/fr not_active Expired
-
1972
- 1972-06-02 US US00259300A patent/US3843661A/en not_active Expired - Lifetime
- 1972-06-02 US US00259299A patent/US3847938A/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4025519A (en) * | 1972-08-07 | 1977-05-24 | Hoechst Aktiengesellschaft | Benzenesulfonyl-ureas |
| US3983107A (en) * | 1973-12-05 | 1976-09-28 | Pfizer Inc. | Hypolipidemic alkenesulfonamides |
| US3897452A (en) * | 1974-08-19 | 1975-07-29 | Merck & Co Inc | Substituted 1,4-dihydro(and 1,2,3,4-tetrahydro)-naphthalen-1,4-imines |
| US4062960A (en) * | 1974-11-06 | 1977-12-13 | Pfizer Inc. | Hypolipidemic alkenesulfonamides |
| US4136180A (en) * | 1976-05-24 | 1979-01-23 | Pfizer Inc. | Hypolipidemic substituted styrenesulfonylureas |
| US4282239A (en) * | 1978-06-27 | 1981-08-04 | Hoechst Aktiengesellschaft | Sulfonyl ureas and pharmaceutical preparations thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| NL6811449A (enrdf_load_stackoverflow) | 1969-02-14 |
| CH516536A (de) | 1971-12-15 |
| OA02879A (fr) | 1970-12-15 |
| US3843661A (en) | 1974-10-22 |
| CH522613A (de) | 1972-05-15 |
| ATA780068A (de) | 1975-02-15 |
| CH522612A (de) | 1972-05-15 |
| FR1585642A (enrdf_load_stackoverflow) | 1970-01-30 |
| GB1230651A (enrdf_load_stackoverflow) | 1971-05-05 |
| AT326139B (de) | 1975-11-25 |
| FR8231M (enrdf_load_stackoverflow) | 1970-09-28 |
| US3847938A (en) | 1974-11-12 |
| BE719374A (enrdf_load_stackoverflow) | 1969-02-12 |
| CH522611A (de) | 1972-05-15 |
| CA961853A (en) | 1975-01-28 |
| LU56669A1 (enrdf_load_stackoverflow) | 1970-02-18 |
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